PROJECT SUMMARY Diseases in the vascular system are still the leading cause of mortality and morbidity in developed countries despite considerable therapeutic progress in recent years. Blood flow velocity provides critical information needed for the diagnosis of vascular diseases, planning of interventional surgery treatment, and monitoring of endovascular treatment of brain arteriovenous malformations. The present lack of knowledge of flow characteristics, arising from the limited temporal and spatial resolution and limited accuracies of the current metrology modalities, averts understanding of the underlying hemodynamics and its correlation with multiple cerebrovascular diseases. To address issues with the current instrumentation, we are developing an ultrafast, high-resolution X-ray blood flow velocimetry system that will provide real time in-vivo quantitative blood velocity maps in the endovascular system. The envisioned system utilizes three transformational technologies; 1) an intense, low cost, pulsed X-ray source with pulse widths down to microseconds and inter-pulse durations of tens of microseconds, 2) an ultrafast X-ray imager with high spatial resolution, large active area, and wide dynamic range, and 3) an X-ray to light converter that overcomes the afterglow and hysteresis limitations of the current high resolution sensors. The system will enable inexpensive digital subtraction angiography (DSA) that can recover precise velocity distribution inside of the vascular systems, especially for complex geometries, making it a unique technology that can be immediately translated into clinical practice. The Phase I research has unequivocally demonstrated the feasibility of developing the proposed system for dynamic blood flow measurements through laboratory experimentation and extensive simulation work. A detailed design of the Phase II system has been accomplished and system evaluation plans have been developed. Specifically, during Phase I we have identified six beta test sites where the Phase II system will be evaluated for various medical applications, the data from which will form a firm foundation for the Phase III commercialization. Considering the commercial potential of the innovative technologies we have filed a US patent application based on the work done so far. This project is highly relevant to NIH's mission because the precise real-time assessment of blood velocities will lead to more educated therapeutic decisions which could save more lives, improve health, and reduce operation cost. The expanded knowledge base will enhance the Nation's economic well-being and ensure a continued high return on the public investment in research.